The long-term goal of the research is to increase our understanding of how synaptic transmission is modulated and regulated. The proposed research will examine excitatory monosynaptic connections between the A and B neurons in the cerebral ganglion of Aplysia which exhibit a novel form of homosynaptic plasticity, slow developing potentiation (SDP). Brief high frequency stimulation (2 sec at 10-30 Hz) of the presynaptic A neurons induces a synapse-specific increase in synaptic efficacy which can last longer than 20 min. Peak potentiation of the EPSP in the postsynaptic B neuron occurs approximately 5 min after the tetanizing train. The proposed research will elucidate the cellular mechanisms mediating SDP. Voltage clamp recordings will be used to determine the basis for the increase in net inward current during the action potential in the presynaptic neurons after SDP induction. Intracellular drug injection will test whether the phosphatidylinositol (inositol triphosphate/ diacylglycerol) second messenger system and protein kinase C mediate SDP. The role of calcium during SDP induction will be investigated. These studies will generate insights into the cellular mechanisms underlying synaptic plasticity and activity-dependent regulation of synaptic transmission.